PROJECT SUMMARY The tsetse fly transmits trypanosomiasis to humans and animals across ~38 countries of Africa. In humans the disease is called African Sleeping Sickness. There is no vaccine to prevent it, and 70 million people are at risk. In animals the disease is called nagana, and it imposes a major economic burden on sub-Saharan Africa. The most effective means of preventing these diseases is to control the tsetse flies that transmit them, and olfactory traps have been particularly useful. Tsetse flies find their human and animal hosts largely through olfactory cues. Better understanding of the tsetse olfactory system may lead to better means of control. This proposal focuses on odorant receptors of the tsetse fly Glossina morsitans, with highest priority accorded to receptors whose expression is well characterized in the tsetse antenna. The experimental plan calls for an analysis of the response profiles of these GmmOr receptors, which will be accomplished by an electrophysiological screen of 130 odorants. Many of these odorants are human or animal host emanations. The panel includes a set of odorants that have previously been tested against the fruit fly Drosophila melanogaster or the malaria mosquito Anopheles gambiae, to facilitate comparison of the G. morsitans receptors with the receptor repertoires of these species. The GmmOr receptors will be tested in an in vivo expression system, the empty neuron system. We will determine whether the receptors are broadly or narrowly tuned, and whether any respond to low concentrations of host odorants. Odorants that elicit strong responses will be tested behaviorally to determine whether they are strong attractants of G. morsitans. Odorants that elicit a strong attractive response at low concentrations may be useful as trapping agents. Olfactory behavior will also be examined as a function of sex and feeding history; several key hypotheses will be tested. The proposal should provide the first detailed functional characterization of odorant receptors in tsetse. The experimental plan is designed to produce valuable new information about the olfactory responses of this fly. The study could also identify new agents useful in controlling tsetse and the diseases that it carries. The proposal will provide training in electrophysiology, molecular biology, genetics, and vector biology to Dr. Shimaa Ebrahim, who has little or no experience in these topics. The project will benefit from an environment that contains a great deal of expertise in insect olfaction. Moreover, Yale is one of the world's centers of tsetse research.